Lactic acidosis not always due to tissue hypoxia: an instructive case report

As a blood marker of tissue hypoxia, lactate is routinely measured to assess and monitor critically ill patients. Hypoperfusion and resulting tissue hypoxia with evolving lactic acidosis is a common feature of many conditions that render patients critically ill. Tissue hypoxia is by no means the only cause of lactic acidosis. 

The term type A lactic acidosis is used to describe lactic acidosis resulting from tissue hypoxia and type B lactic acidosis is used to describe lactic acidosis occurring in the context of adequate perfusion and well-oxygenated tissues. There are many causes of type B (non-hypoxic) lactic acidosis, including malignant disease. 

Whilst lactic acidosis occurring in the critically ill is almost always due to tissue hypoxia (i.e. type A lactic acidosis), that is not necessarily the sole cause. A recently published case history reminds that alternative causes of lactic acidosis (i.e. those that cause type B lactic acidosis) should be considered in critically ill patients, particularly when lactic acidosis does not resolve after resuscitation. 

The case concerns a 73-year-old lady with a history of type 2 diabetes and hypertension who was admitted to hospital for investigation following presentation of abdominal pain, nausea, vomiting, diarrhea and weight loss. Her lactate at this time was elevated (4.9 mmol/L) and bicarbonate was reduced (11 mmol/L) with high anion gap, indicating acidosis. 

After 2 weeks of intensive investigation, during which the lady suffered an episode of hematemesis which was attributed to “stable” ulcers visualized during endoscopic examination, no definitive diagnosis had been made. Still suffering the symptoms that brought her to hospital the lady was frustrated and left the hospital against medical advice. Her lactate at this time was even higher (14.5 mmol/L) and remained unexplained. 

The next day the patient was urgently readmitted in a shocked, critically ill state after being found in a pool of blood with altered mental status. She was hypotensive (BP 101/47) with increased heart rate (115 beats per min). Reduced hematocrit (21 %) reflected significant blood loss. Lactate was now 25 mmol/L. Blood gas analysis revealed severe acidosis and hypoxemia (pH 6.8, pO₂ 43 mmHg/5.7 kPa). The lady was given transfusion (2 units of red cells) and was intubated prior to urgent referral to a tertiary care hospital for intensive care and endoscopic treatment of the bleeding ulcers that had caused her readmission. 

With correction of fluid loss and resuscitation from the shocked state induced by peptic ulcer bleed, the lady’s lactate reduced significantly (to a nadir of 4.9 mmol/L) but later rose again (9.4 mmol/L). Sepsis was suspected, prompting antibiotic treatment and CT scan in the search for a source of presumed infection. This CT scan eventually led to an explanation for the raised lactate that had been found at the initial hospital admission and contributed to the rising lactate that featured during her “critically ill” second admission. 

The lady was found to have lung cancer (small cell carcinoma) with suspicious evidence of tumor spread to the liver. Chemotherapy was recommended but the lady declined treatment and sadly passed away after a period of “comfort-only” care. Despite hemodynamic stability throughout this period, her lactate remained resolutely raised and was 16.5 mmol/L on the day she died. 

The authors of this case study imply that the lady was suffering type B lactic acidosis due to malignancy at her first hospital visit; a combination of type A and type B lactic acidosis during resuscitation from hypovolemic shock induced by massive hemorrhage; and type B lactic acidosis due to malignancy for the remaining days of her life. In discussion of the case, the authors outline current understanding of the pathophysiology of type B lactic acidosis in malignancy.